Recently iron chelates capable of reversibly binding oxygen at physiologic temperatures have been synthesized. These relatively low molecular weight compounds afford an alternative to liquid fluorocarbons in the development of artificial blood substitutes. The fluorocarbon- containing substitutes have been used successfully for the complete replacement of the blood of living rats. There is every reason to believe similar success can be obtained with iron chelate-containing preparations. An advantage of the chelates is that they function efficiently at low partial pressures oxygen. The presently proposed research will be conducted in collaboration with Dr. Jack Baldwin of MIT who will carry out the synthesis of the iron chelates for use in these biologic studies. Because they are small molecules two approaches will be employed to prolong their halflife in circulation following their intravenous administration. One will be to attach the chelates to large molecules such as hydroxyethyl starch. The other is to modify the chelates to enhance their solubility in non-polar liquids such as fluorocarbons or lipids. Such chelate-containing liquids could then be dispersed as fluorocarbons themselves are now being dispersed. Artificial blood substitutes based on an iron chelate-fluorocarbon gas transport system would allow an optimum oxygen carrying capacity at both low and high partial pressures of oxygen. Development of artificial blood substitutes containing reversible oxygen-binding chelates will find widespread practical and experimental bio-medical applications both in vivo and in vitro. Such substitutes long searched for can now become a reality.